title: Psoriatic keratinocytes are resistant to tumor necrosis factor alpha's induction of mRNA for the NMDA-R2C subunit.
abstract: Psoriatic individuals demonstrate accelerated healing and the Koebner phenomenon, suggesting that psoriatic proliferation of keratinocytes is not inhibited appropriately after skin injury. Serial analysis of gene expression in TNFα-exposed keratinocytes shows the greatest alteration in expression of NMDA-R2C. Expression of the NMDA receptor is altered in diseased skin containing TNFα, and TNFα plays a prominent role in psoriasis. An abnormality in induction of NMDA-R2C by TNFα in psoriatic keratinocytes may explain their lack of growth inhibition. We compared the capacity of TNFα to induce expression of NMDA-R2C in normal and psoriatic (involved and uninvolved) keratinocytes in vitro. After 72 h of incubation with TNFα, normal keratinocytes demonstrated a significant induction of NMDA-R2C mRNA compared with control cultures, whereas psoriatic keratinocytes showed no induction. In an in vitro model of wounding (scratches on monolayers), TNFα inhibited migration/proliferation of keratinocytes only at the edge of NMDA-R2C expressing wounded monolayers of normal keratinocytes.
authors.affiliation: UCSD, San Diego, CA, USA.
authors.forename: Vera B
authors.initials: VB
authors.lastname: Morhenn
authors.forename: William J
authors.initials: WJ
authors.lastname: Nahm
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Mansbridge
mesh_terms: D000328:Adult; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000166:cytology*; D008297:Male; D011565:Psoriasis / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014945:Wound Healing
chemical_list: C432823:NR2C NMDA receptor; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D014409:Tumor Necrosis Factor-alpha
keywords: NMDA receptor; TNFα; keratinocytes; psoriasis